Rare Variants in Genes Encoding Subunits of the Epithelial Na + Channel Are Associated With Blood Pressure and Kidney Function.

Autor:	Blobner BM; Division of Gastroenterology, Hepatology, and Nutrition (B.M.B.), University of Pittsburgh, Pittsburgh' PA., Kirabo A; Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (A.K.)., Kashlan OB; Renal-Electrolyte Division (O.B.K., S.S., T.R.K.), University of Pittsburgh, Pittsburgh' PA.; Department of Medicine, Department of Computational and Systems Biology (O.B.K.), University of Pittsburgh, Pittsburgh' PA., Sheng S; Renal-Electrolyte Division (O.B.K., S.S., T.R.K.), University of Pittsburgh, Pittsburgh' PA., Arnett DK; College of Public Health, University of Kentucky, Lexington' KY (D.K.A.)., Becker LC; GeneSTAR Research Program, Division of Cardiology, Department of Medicine (L.C.B.), Johns Hopkins University School of Medicine, Baltimore, MD., Boerwinkle E; Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston' Houston' TX (E.B.).; Human Genome Sequencing Center (E.B., R.A.G., V.K.M.), Baylor College of Medicine, Houston, TX., Carlson JC; Department of Biostatistics, (J.C.C., D.E.W.), University of Pittsburgh, Pittsburgh' PA.; Department of Human Genetics, (J.C.C., D.E.W., R.L.M.), University of Pittsburgh, Pittsburgh' PA., Gao Y; Department of Medicine, University of Mississippi Medical Center, Jackson' MS (Y.G.)., Gibbs RA; Human Genome Sequencing Center (E.B., R.A.G., V.K.M.), Baylor College of Medicine, Houston, TX.; Department of Molecular and Human Genetics (R.A.G.), Baylor College of Medicine, Houston, TX., He J; Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA (J.H., T.K.N., X.S.).; Tulane University Translational Science Institute, New Orleans, LA (J.H., T.N.K.)., Irvin MR; Department of Epidemiology, University of Alabama at Birmingham' Birmingham' AL (M.R.I.)., Kardia SLR; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor' MI (S.L.R.K., J.A.S.)., Kelly TN; Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA (J.H., T.K.N., X.S.).; Tulane University Translational Science Institute, New Orleans, LA (J.H., T.N.K.)., Kooperberg C; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA (C.K., A.P.R.)., McGarvey ST; Department of Epidemiology and International Health Institute, Brown University School of Public Health, Providence, RI (S.T.M., T.N.)., Menon VK; Human Genome Sequencing Center (E.B., R.A.G., V.K.M.), Baylor College of Medicine, Houston, TX., Montasser ME; Department of Medicine, University of Maryland, Baltimore' MD (M.E.M.)., Naseri T; Department of Epidemiology and International Health Institute, Brown University School of Public Health, Providence, RI (S.T.M., T.N.).; Ministry of Health, Apia, Samoa (T.N.)., Redline S; Division of Sleep and Circadian Disorders, Department of Medicine, Brigham and Women's Hospital, Boston, MA (S.R.).; Harvard Medical School, Boston, MA (S.R.).; Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA (S.R.)., Reiner AP; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA (C.K., A.P.R.)., Reupena MS; Lutia i Puava 'ae Mapu i Fagalele, Apia, Samoa (M.S.R.)., Smith JA; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor' MI (S.L.R.K., J.A.S.)., Sun X; Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA (J.H., T.K.N., X.S.)., Vaidya D; GeneSTAR Research Program, Division of General Internal Medicine, Department of Medicine (D.V., L.R.Y.), Johns Hopkins University School of Medicine, Baltimore, MD.; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (D.V.)., Viaud-Martinez KA; Illumina Laboratory Services, Illumina Inc, San Diego, CA (K.A.V.-M.)., Weeks DE; Department of Biostatistics, (J.C.C., D.E.W.), University of Pittsburgh, Pittsburgh' PA.; Department of Human Genetics, (J.C.C., D.E.W., R.L.M.), University of Pittsburgh, Pittsburgh' PA., Yanek LR; GeneSTAR Research Program, Division of General Internal Medicine, Department of Medicine (D.V., L.R.Y.), Johns Hopkins University School of Medicine, Baltimore, MD., Zhu X; Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH (X.Z.)., Minster RL; Department of Human Genetics, (J.C.C., D.E.W., R.L.M.), University of Pittsburgh, Pittsburgh' PA., Kleyman TR; Renal-Electrolyte Division (O.B.K., S.S., T.R.K.), University of Pittsburgh, Pittsburgh' PA.; Department of Cell Biology, (T.R.K.), University of Pittsburgh, Pittsburgh' PA.; Department of Pharmacology and Chemical Biology, (T.R.K.), University of Pittsburgh, Pittsburgh' PA.
Jazyk:	angličtina
Zdroj:	Hypertension (Dallas, Tex. : 1979) [Hypertension] 2022 Nov; Vol. 79 (11), pp. 2573-2582. Date of Electronic Publication: 2022 Oct 04.
DOI:	10.1161/HYPERTENSIONAHA.121.18513
Abstrakt:	Background: The epithelial Na + channel (ENaC) is intrinsically linked to fluid volume homeostasis and blood pressure. Specific rare mutations in SCNN1A , SCNN1B , and SCNN1G , genes encoding the α, β, and γ subunits of ENaC, respectively, are associated with extreme blood pressure phenotypes. No associations between blood pressure and SCNN1D , which encodes the δ subunit of ENaC, have been reported. A small number of sequence variants in ENaC subunits have been reported to affect functional transport in vitro or blood pressure. The effects of the vast majority of rare and low-frequency ENaC variants on blood pressure are not known. Methods: We explored the association of low frequency and rare variants in the genes encoding ENaC subunits, with systolic blood pressure, diastolic blood pressure, mean arterial pressure, and pulse pressure. Using whole-genome sequencing data from 14 studies participating in the Trans-Omics in Precision Medicine Whole-Genome Sequencing Program, and sequence kernel association tests. Results: We found that variants in SCNN1A and SCNN1B were associated with diastolic blood pressure and mean arterial pressure ( P <0.00625). Although SCNN1D is poorly expressed in human kidney tissue, SCNN1D variants were associated with systolic blood pressure, diastolic blood pressure, mean arterial pressure, and pulse pressure ( P <0.00625). ENaC variants in 2 of the 4 subunits ( SCNN1B and SCNN1D ) were also associated with estimated glomerular filtration rate ( P <0.00625), but not with stroke. Conclusions: Our results suggest that variants in extrarenal ENaCs, in addition to ENaCs expressed in kidneys, influence blood pressure and kidney function.
Databáze:	MEDLINE
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